title: Mechanosignaling in bone health, trauma and inflammation.
abstract: CONCLUSIONS
  Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms.
  
  
  BACKGROUND
  In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade.
  
  
  RESULTS
  Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone.
  
  
  CONCLUSIONS
  Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health.
authors.affiliation: 1 Department of Orthopaedic Surgery, The Ohio State University College of Medicine , Columbus, Ohio.
authors.forename: Derrick M
authors.initials: DM
authors.lastname: Knapik
authors.forename: Priyangi
authors.initials: P
authors.lastname: Perera
authors.forename: Jin
authors.initials: J
authors.lastname: Nam
authors.forename: Alisa D
authors.initials: AD
authors.lastname: Blazek
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
authors.forename: Binnaz
authors.initials: B
authors.lastname: Leblebicioglu
authors.forename: Hiranmoy
authors.initials: H
authors.lastname: Das
authors.forename: Lai Chu
authors.initials: LC
authors.lastname: Wu
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Hewett
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Robling
authors.forename: David C
authors.initials: DC
authors.lastname: Flanigan
authors.forename: Beth S
authors.initials: BS
authors.lastname: Lee
authors.forename: Sudha
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D016328:NF-kappa B